Currently, every year 21 million people worldwide suffer from serious injuries resulting in severe blood loss, and more than one third of these cases lead to death. (See Bledsoe, B. E. “The Golden Hour: Fact or Fiction.” Emergency Med. Serv. 6, 105 (2002), which is herein incorporated by reference in its entirety.) Among these patients are American soldiers in Iraq whose fatality rate with severe injuries is 90%. Uncontrolled hemorrhaging from these injuries is the leading cause of preventable combat deaths among U.S. soldiers in Iraq. According to the Marine Corps registry, 45-60% of combat casualty deaths are due to potentially preventable uncontrolled hemorrhage. (See Clarke, Patrick E. “Z-Medica's Products Cited as Life Saving on Battlefield”, which is herein incorporated by reference in its entirety.) Similarly, uncontrolled hemorrhage is the leading cause of potentially preventable deaths in the U.S. with 30-40% of all trauma deaths in the civilian population due to uncontrolled bleeding. In many cases, these deaths occur before the injured are able to be transported to medical treatment with approximately 40% of civilian and 90% of military casualties occurring before the patients reach a treatment facility. (See Kim, Seung-Ho M D; Stezoski, S. William; Safar, Peter M D; Capone, Antonio M D; Tisherman, Samuel M D. Journal of Trauma-Injury Infection & Critical Care. 42(2):213-222, February 1997, which is herein incorporated by reference in its entirety.) Many of these casualties can be prevented if an effective treatment is used to quickly stop the significant loss of blood.
Controlling hemorrhage is also a critical issue in medical facilities with 97 million patients experiencing surgical bleeding every year worldwide. (See B. S. Kheirabadi, E. M. Acheson, R. Deguzman, J. L. Sondeen, K. L. Ryan, A. Delgado, E. L. Dick, J. B. Holcomb, “Hemostatic efficacy of two advanced dressings in an aortic hemorrhage model in swine.” J. Trauma. (2005), which is herein incorporated by reference in its entirety.) Despite advances in medical technology, hemorrhage control is still a major problem in emergency medical care. In the first 48 hours of hospitalization, approximately 51% of deaths are due to hemorrhage (See F W Verheugt, M J van Eenige, J C Res, M L Simoons, P W Serruys, F Vermeer, D C van Hoogenhuyze, P J Remme, C de Zwaan, and F Baer. Bleeding complications of intracoronary fibrinolytic therapy in acute myocardial infarction. Assessment of risk in a randomised trial, which is herein incorporated by reference it its entirety.)
Improving the ability to control hemorrhage for injuries that are otherwise survivable would greatly reduce trauma mortality, and this knowledge has encouraged numerous advancements in hemostatic control; however, the currently available hemostatic bandages are not sufficiently resistant to termination in high blood flow and they do not have strong enough adhesive properties to stop severe blood flow for an adequate time period.
Today the application of continuous pressure using gauze bandages remains the primary technique used to stanch blood flow, particularly in severe bleeding wounds. This procedure neither successfully nor safely stops severe blood flow. As in the past, this method continues to be a major survival problem in the case of serious life-threatening bleeding. Other currently available hemostatic bandages, such as collagen wound dressings or dry fibrin thrombin wound dressings do not have strong enough adhesive properties to serve any realistic purpose in the stanching of severe blood flow. These hemostatic bandages are also fragile and are therefore liable to fail if damaged due to bending or application of pressure. (See Gregory, Kenton W. and Simon J. McCarthy. Wound dressings, apparatus, and methods for controlling severe, life-threatening bleeding, which is herein incorporated by reference in its entirety.)
Recent advancement in hemostatic bandages have targeted the immediate treatment of acute wounds, such as the prevention of casualties due to hemorrhage on the battlefield. Chitosan based bandages have been approved and used in numerous settings including battlefield use with success. Chitosan is an amino-polysaccharide that is commercially produced from the deacetlyation of chitin which is an abundant natural biopolymer that is found in the exoskeleton of crustaceans. Advantages of chitosan as a material for wet wound dressings include its ability to accelerate wound-healing, its hemostatic properties, its stimulation of macrophage activity, and its general anti-microbial impact which helps prevent infection at the wound site. Chitosan is used as a hemostatic agent because of its cationic nature. Since the surfaces of most biological cells are anionic, including red blood cells, chitosan strongly adheres to the cells of tissue at wound sites because of an electrostatic interaction and is able to initially halt blood flow. (See Dornard, Alain and Monique. “Chitosan: Structure-Properties Relationship and Biomedical Applications.” (2002), which is herein incorporated by reference it its entirety.)
Despite the advantages of using a chitosan-based dressing, there are also significant disadvantages. In a study conducted in 2005 by Kheirabadi et al, researchers caused injury to the aorta of pigs and attempted to control hemorrhage using the Hemostatic HemConÂ® Bandage. The results of the study showed that though the chitosan bandage effectively reached hemostasis immediately after its application, secondary bleeding resumed approximately 2 hours later and resulted in the death of the pigs. They found that the adhesion between the bandage and the tissue decreased as the bandaged became saturated with blood. (See B. S. Kheirabadi, E. M. Acheson, R. Deguzman, J. L. Sondeen, K. L. Ryan, A. Delgado, E. L. Dick, J. B. Holcomb, “Hemostatic efficacy of two advanced dressings in an aortic hemorrhage model in swine.” J. Trauma. (2005), which is herein incorporated by reference in its entirety.) In realistic situations in which patients are incapable of reaching adequate medical treatment, such as on the battlefield, this time period is too short and the Hemostatic HemConÂ® Bandage would be an insufficient hemostatic agent.
Wound physiology is difficult to manipulate due to the complexity of cell-to-cell signaling networks which communicate during wound healing, but fortunately for healthy individuals, severe wounds can be healed quite well by simply disinfecting the wound area and stopping the loss of blood by suturing the open, damaged tissue. However, in many cases of acute wounds, internal or external, suturing is neither effective nor practical. In these cases, it is advantageous to use solid materials which adhere strongly enough to tissue such that they provide a seal upon pressing such materials onto the damaged tissue, thus preventing the loss of blood within the boundaries of the seal.
Additionally, blood clotting is a necessary aspect of wound physiology, and in many practical cases it is highly valuable for survival. However, for human beings and most mammals, the ability for blood to clot is limited because a significant increase in the ability of healthy mammalian organisms to form blood clots would most likely result in death of the organism as a result of any minor internal injury. In such cases, clots would form at the site of the injury, enter into the blood stream and eventually cause a stroke or heart failure due to blockage of important blood vessels. Because clotting ability must be limited under normal physiological conditions, in the case of acute wounds, which refers to a fast impact injury resulting in a high rate of blood loss, clotting is not a legitimate means to provide hemostasis. Therefore, acute wounds typically drain blood banks of their stocks as large blood transfusions are required to keep patients alive during transport to treatment facilities and subsequently during the surgery required to close the wound.
Therefore, it would be desirable to provide a strongly adhesive hemostatic bandage that promotes increased adhesion to wounded tissue or cells. It would also be desirable to provide a strongly adhesive flowable spray solution or surgical sealant to stop minor bleeding and to seal tissues in surgical applications.